全文获取类型
收费全文 | 13465篇 |
免费 | 1041篇 |
国内免费 | 830篇 |
专业分类
15336篇 |
出版年
2024年 | 29篇 |
2023年 | 137篇 |
2022年 | 331篇 |
2021年 | 600篇 |
2020年 | 368篇 |
2019年 | 482篇 |
2018年 | 426篇 |
2017年 | 332篇 |
2016年 | 492篇 |
2015年 | 821篇 |
2014年 | 880篇 |
2013年 | 1050篇 |
2012年 | 1218篇 |
2011年 | 1040篇 |
2010年 | 637篇 |
2009年 | 568篇 |
2008年 | 776篇 |
2007年 | 606篇 |
2006年 | 615篇 |
2005年 | 488篇 |
2004年 | 413篇 |
2003年 | 347篇 |
2002年 | 290篇 |
2001年 | 273篇 |
2000年 | 227篇 |
1999年 | 220篇 |
1998年 | 156篇 |
1997年 | 126篇 |
1996年 | 136篇 |
1995年 | 129篇 |
1994年 | 115篇 |
1993年 | 94篇 |
1992年 | 134篇 |
1991年 | 117篇 |
1990年 | 81篇 |
1989年 | 102篇 |
1988年 | 60篇 |
1987年 | 49篇 |
1986年 | 59篇 |
1985年 | 65篇 |
1984年 | 18篇 |
1983年 | 24篇 |
1982年 | 28篇 |
1981年 | 13篇 |
1980年 | 25篇 |
1979年 | 20篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1974年 | 9篇 |
1972年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Chun Xia Liu Wen Long Wang Rui Yuan Zhao Hai Tao Wang Yi Yi Liu Shen Yuan Wang Huan Min Zhou 《In vitro cellular & developmental biology. Animal》2014,50(3):207-213
This study was performed to culture and preliminarily identify the primordial germ cells (PGCs) isolated from the genital ridge of the Mongolian sheep fetus. The growth characteristics of the sheep PGCs were detected in different culture systems such as culture media, resources, and state and passages of feeder cells. The obtained embryonic germ (EG) cells were identified by morphology, enzymology, and immunofluorescence. The results showed that the sheep EG cell colonies were ridgy, typically nest like, and compact, and had regular edges. Alkaline phosphatase staining reaction was weakly positive. EG cells expressed Kit, Rex-1, Nanog, and Oct-4. Immunofluorescence detection was weakly positive for Oct3/4, whereas positive for SSEA-1, SSEA-3, SSEA-4, TRA-1-61, and TRA-1-80. 相似文献
992.
Yanhua Li Yuan Shen Chao Cai Chenchun Zhong Lei Zhu Ming Yuan Haiyun Ren 《The Plant cell》2010,22(8):2710-2726
Formins have long been known to regulate microfilaments but have also recently been shown to associate with microtubules. In this study, Arabidopsis thaliana FORMIN14 (AFH14), a type II formin, was found to regulate both microtubule and microfilament arrays. AFH14 expressed in BY-2 cells was shown to decorate preprophase bands, spindles, and phragmoplasts and to induce coalignment of microtubules with microfilaments. These effects perturbed the process of cell division. Localization of AFH14 to microtubule-based structures was confirmed in Arabidopsis suspension cells. Knockdown of AFH14 in mitotic cells altered interactions between microtubules and microfilaments, resulting in the formation of an abnormal mitotic apparatus. In Arabidopsis afh14 T-DNA insertion mutants, microtubule arrays displayed abnormalities during the meiosis-associated process of microspore formation, which corresponded to altered phenotypes during tetrad formation. In vitro biochemical experiments showed that AFH14 bound directly to either microtubules or microfilaments and that the FH2 domain was essential for cytoskeleton binding and bundling. However, in the presence of both microtubules and microfilaments, AFH14 promoted interactions between microtubules and microfilaments. These results demonstrate that AFH14 is a unique plant formin that functions as a linking protein between microtubules and microfilaments and thus plays important roles in the process of plant cell division. 相似文献
993.
Du X Shen J Kugan N Furth EE Lombard DB Cheung C Pak S Luo G Pignolo RJ DePinho RA Guarente L Johnson FB 《Molecular and cellular biology》2004,24(19):8437-8446
The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome. 相似文献
994.
Association between the change in body mass index from early adulthood to midlife and subsequent type 2 diabetes mellitus 下载免费PDF全文
Yiming Mu Chao Liu Jiajun Zhao Lulu Chen Qiang Li Tao Yang Li Yan Qin Wan Shengli Wu Yan Liu Guixia Wang Zuojie Luo Xulei Tang Gang Chen Yanan Huo Zhengnan Gao Qing Su Youmin Wang Guijun Qin Huacong Deng Xuefeng Yu Feixia Shen Li Chen Liebin Zhao Jichao Sun Lin Ding Yu Xu Min Xu Meng Dai Tiange Wang Di Zhang Jieli Lu Yufang Bi Shenghan Lai Donghui Li Weiqing Wang Guang Ning 《Obesity (Silver Spring, Md.)》2016,24(3):703-709
995.
Shen YH Godlewski J Bronisz A Zhu J Comb MJ Avruch J Tzivion G 《Molecular biology of the cell》2003,14(11):4721-4733
14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed against a degenerated mode-1 14-3-3 binding motif (RSxpSxP), we demonstrate that most of the 14-3-3-associated proteins in COS-7 cells are phosphorylated on sites that react with this antibody. The binding of these phosphoproteins depends on 14-3-3 dimerization, inasmuch as proteins associated in vivo with a monomeric 14-3-3 form are not recognized by the phospho-specific antibody. The role of 14-3-3 dimerization in the phosphorylation-dependent target binding is further exemplified with two well-defined 14-3-3 targets, Raf and DAF-16. Raf and DAF-16 can bind both monomeric and dimeric 14-3-3; however, whereas phosphorylation of specific Raf and DAF-16 sites is required for binding to dimeric 14-3-3, binding to monomeric 14-3-3 forms is entirely independent of Raf and DAF-16 phosphorylation. We also find that dimerization diminishes 14-3-3 susceptibility to phosphorylation. These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other. 相似文献
996.
The cold-active lipase gene Lip-948, cloned from Antarctic psychrotrophic bacterium Psychrobacter sp. G, was ligated into plasmid pColdI. The recombinant plasmid pColdI+Lip-948 was then transformed into Escherichia coli BL21. SDS-PAGE analysis showed that there was substantive expression of lipase LIP-948 in E. coli with a yield of about 39% of total protein, most of which was present in the inclusion body. The soluble protein LIP-948 only consisted of 1.7% of total LIP-948 with a specific activity of 66.51U/mg. Co-expression of molecular chaperones with the pColdI+Lip-948 were also carried out. The results showed that co-expression of different chaperones led to an increase or decrease in the formation of soluble LIP-948 in varying degrees. Co-expression of pColdI+Lip-948 with chaperone pTf16 and pGro7 decreased the amount of soluble LIP-948, while the soluble expression was enhanced when pColdI+Lip-948 was co-expressed with "chaperone team" plasmids (pKJE7, pG-Tf2, pG-KJE8), respectively. LIP-948 was most efficiently expressed in soluble form when it was co-expressed with pG-KJE8, which was up to 19.8% of intracellular soluble proteins and with a specific activity of 108.77U/mg. The soluble LIP-948 was purified with amylase affinity chromatography and its enzymatic characters were studied. The optimal temperature and pH of LIP-948 was 35°C and 8, respectively. The activity of LIP-948 dropped dramatically after incubation at 50°C for 15min and was enhanced by Sr(2+), Ca(2+). It preferentially hydrolyzed 4-nitrophenyl esters with the shorter carbon chain. 相似文献
997.
Bing‐Qing Xiong Xinwei Zhou Gui‐Liang Xu Yuzi Liu Likun Zhu Youcheng Hu Shou‐Yu Shen Yu‐Hao Hong Si‐Cheng Wan Xiao‐Chen Liu Xiang Liu Shengli Chen Ling Huang Shi‐Gang Sun Khalil Amine Fu‐Sheng Ke 《Liver Transplantation》2020,10(4)
Alloy materials such as Si and Ge are attractive as high‐capacity anodes for rechargeable batteries, but such anodes undergo severe capacity degradation during discharge–charge processes. Compared to the over‐emphasized efforts on the electrode structure design to mitigate the volume changes, understanding and engineering of the solid‐electrolyte interphase (SEI) are significantly lacking. This work demonstrates that modifying the surface of alloy‐based anode materials by building an ultraconformal layer of Sb can significantly enhance their structural and interfacial stability during cycling. Combined experimental and theoretical studies consistently reveal that the ultraconformal Sb layer is dynamically converted to Li3Sb during cycling, which can selectively adsorb and catalytically decompose electrolyte additives to form a robust, thin, and dense LiF‐dominated SEI, and simultaneously restrain the decomposition of electrolyte solvents. Hence, the Sb‐coated porous Ge electrode delivers much higher initial Coulombic efficiency of 85% and higher reversible capacity of 1046 mAh g?1 after 200 cycles at 500 mA g?1, compared to only 72% and 170 mAh g?1 for bare porous Ge. The present finding has indicated that tailoring surface structures of electrode materials is an appealing approach to construct a robust SEI and achieve long‐term cycling stability for alloy‐based anode materials. 相似文献
998.
Ma J Zhang L Han W Shen T Ma C Liu Y Nie X Liu M Ran Y Zhu D 《Journal of lipid research》2012,53(6):1093-1105
Pulmonary artery endothelial plexiform lesion is responsible for pulmonary vascular remodeling (PVR), a basic pathological change of pulmonary arterial hypertension (PAH). Recent evidence suggests that epoxyeicosatrienoic acid (EET), which is derived from arachidonic acid by cytochrome p450 (CYP) epoxygenase, has an essential role in PAH. However, until now, most research has focused on pulmonary vasoconstriction; it is unclear whether EET produces mitogenic and angiogenic effects in pulmonary artery endothelial cells (PAEC). Here we found that 500 nM/l 8,9-EET, 11,12-EET, and 14,15-EET markedly augmented JNK and c-Jun activation in PAECs and that the activation of c-Jun was mediated by JNK, but not the ERK or p38 MPAK pathway. Moreover, treatment with 8,9-EET, 11,12-EET, and 14,15-EET promoted cell proliferation and cell-cycle transition from the G0/G1 phase to S phase and stimulated tube formation in vitro. All these effects were reversed after blocking JNK with Sp600125 (a JNK inhibitor) or JNK1/2 siRNA. In addition, the apoptotic process was alleviated by three EET region isomers through the JNK/c-Jun pathway. These observations suggest that 8,9-EET, 11,12-EET, and 14,15-EET stimulate PAEC proliferation and angiogenesis, as well as protect the cells from apoptosis, via the JNK/c-Jun pathway, an important underlying mechanism that may promote PAEC growth and angiogenesis during PAH. 相似文献
999.
Peng Zhong Jianye Peng Yewen Hu Jun Zhang Caijie Shen 《Journal of cellular and molecular medicine》2022,26(21):5369
MOTS‐c, a mitochondrial‐derived peptide (MDP), has been shown to have multiple biological activities such as antioxidation, anti‐inflammation, and anti‐apoptosis properties. In the present study, we aimed at evaluating the therapeutic effect of MOTS‐c peptide in an animal model of heart failure. The heart failure mouse model was made by transverse aortic constriction (TAC) operations. The MOTS‐c peptide was administrated subcutaneously by using an osmotic pump. At the end of the animal experiment, cardiac function was evaluated by echocardiography, and heart tissues were subjected to histological and molecular analysis. In vitro cultured H9C2 cells were used to test the effects of MOTS‐c overexpression on cell death in response to H2O2 stimulation. Our study showed that MOTS‐c peptide attenuated TAC‐induced cardiac dysfunction and remodelling. In addition, the MOTS‐c peptide reduced the inflammatory response and upregulated the antioxidant capacity, coupled with the activation of the AMPK pathway in the heart of the TAC mouse model. In in vitro cultured cardiac cells, overexpression of MOTS‐c was shown to activate the AMPK pathway and protect cell apoptosis in response to H2O2 stimulation. Taken together, our study suggested that MOTS‐c peptides may have therapeutic potential in treating HF. 相似文献
1000.
Huanan Wen Jiaxin Zhong Bei Shen Tao Gan Chao Fu Zhihong Zhu Rui Li Xu Yang 《生物学前沿》2013,8(4):444-450
To compare the cytotoxicity on HeLa cells induced by nanosized and microsized tellurium powders, HeLa cells were exposed to different concentrations of tellurium powders (0, 50, 100, 150 and 200 μg/mL) for 12 h. In this study, detection of a series of biomarkers, including reactive oxygen species (ROS), glutathione (GSH), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in addition to DNA and protein crosslink (DPC) and MTTassay, were conducted to evaluate the cytotoxicity. It is indicated that compared with the control group, there was no significant difference in the induced cytotoxicity at concentrations lower than 50 μg/mL for both nanosized and microsized tellurium powders. While there appears a significant difference in the induced cytotoxicity for nanosized tellurium powders when the concentration is higher than 100 μg/mL as well as for microsized tellurium powders when the concentration is higher than 200 μg/mL. Moreover, it is found that the cytotoxicity induced on HeLa cells exhibits a certain dose-effect relationship with the concentration of tellurium powders. A conclusion has been reached that the toxicity on HeLa cells can be induced by both nanosized and microsized tellurium powders, and the toxicity of the nanosized tellurium powders is significantly greater than the microsized one. 相似文献